DESCRIPTION: The National Center for Microscopy and Imaging Research (NCMIR) was established to develop computer aided advanced microscopy for acqusition of structural and functional data in the dimensional range of 1 nm3 to 100 um3. With novel specimen staining methods, imaging instruments and computational capabilities, researchers are addressing the next great biological challenges in the post-genomic age by situating proteins and macromolecular complexes in their cellular and tissue environements. Resource instruments include intermediate high voltage transmission electron microscopes (IVEMs) and high-speed large-format laser-scanning light microscopes specially modified for "meso-scale" biological microscopy. Our core technological research is directed towards developing technologies that will contribute to structural neurobiology, cell and molecular biology. With NCMIR's participation in the Biomedical Informatics Research Network (BIRN), we are scaling up our ability to image at high resolution across wide expanses of brain tissue to reveal structural and molecular in mouse models of human disease. Our collaboration, service, training and dissemination programs expand the use of these technologies to maximize their value to the biomedical community. Core biological projects include development of new staining methods for IVEM and for correlated light and IVEM analyses of specimens to examine the architecture of neuronal systems and the dynamics of subcellular processes. Core research is tightly linked to collaborative projects, in areas such as animal of neurodegenerative diseases, stroke, heart disease, cancer, infectious diseases and diabetes. The capabilites and research accomplishments anticipated in specimen preparation are augmented by continued development of instruments and image processing facilities. We emphasize the use of computer-aided methods for enhancing image contrast and reconstructing larger structural complexes using 3D tomographic and serial thick section analysis. Extraction of 3D information on a large scale will be accelerated through the development of high-throughput methods for tomographic reconstruction, analysis and visualization. We continue to provide researchers greater access to the Resource through development of web-based remote control systems for the IVEM's and interfaces for computational grids and distributed databases via high-speed networks. We will expand outreach efforts via web-based tutorials, software and microscopic data repositories linked to other biological databases.